Nationwide use of prescription opioids quadrupled to more than 240 million prescriptions per year between 1999 to 2010. This increase has been accompanied by an alarming rise in opioid misuse and abuse, addiction, and fatal and nonfatal overdoses. In response to this growing national epidemic, the Department of Health and Human Services has called for the creation of clear opioid prescribing guidelines and further developing the evidence base to guide opioid prescribing for the management of pain. To date, guidelines have largely focused on opioid use in younger adults despite the unique issues facing older adults (?65 years old) including a large burden of pain, extensive analgesics use, and recent increase in drug overdose-related deaths in the elderly population. Prior guidelines have provided no direction regarding appropriate opioid use to treat pain in nursing home residents. This is problematic due to the high prevalence of chronic pain in nursing home residents as well as age-related vulnerability to adverse drug events due to changes in pharmacokinetics/pharmacodynamics and higher prevalence of multiple comorbidities and polypharmacy in this population as compared to noninstitutionalized older adults. Using an in-house national repository of Minimum Data Set 3.0 ? a federally required clinical assessment of all residents in Medicare or Medicaid certified nursing homes ? merged to Medicare Part A and D and facility-level characteristics in CASPER (Certification and Survey Provider and Enhanced Reporting) from 2011-2013, this proposal addresses the evidence gap in safe opioid use in US nursing home residents with three specific aims: 1) to identify sociodemographic, clinical, and facility-level correlates of opioid use in terms of duration of use (acute vs. chronic), duration of action (short- vs. long-acting), and dose in ?morphine equivalents?; 2) to estimate the incidence of opioid-related drug overdoses and identify resident- and drug regimen-related risk factors for opioid overdose; and 3) to evaluate the comparative safety of specific commonly-initiated opioids in terms of serious adverse health outcomes (all-cause mortality, hospitalization for cardiovascular disease, fractures, and bowel obstruction). Methodological innovations include the use of multilevel modeling and targeted maximum likelihood estimation approaches. This proposal is directly relevant to the approximately 1.4 million older adults living in US nursing homes on any given day ? many of whom will receive opioids while institutionalized. The knowledge generated will inform stakeholders on how opioids are used in this population, the risk of overdose when using opioids, and the comparative safety of short- and long- term use of commonly initiated opioids in the nursing home setting.